Chatuphonprasert Waranya, Jarukamjorn Kanokwan, Ellinger Isabella
Pathophysiology of the Placenta, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Faculty of Medicine, Mahasarakham University, Maha Sarakham, Thailand.
Front Pharmacol. 2018 Sep 12;9:1027. doi: 10.3389/fphar.2018.01027. eCollection 2018.
The steroid hormones progestagens, estrogens, androgens, and glucocorticoids as well as their precursor cholesterol are required for successful establishment and maintenance of pregnancy and proper development of the fetus. The human placenta forms at the interface of maternal and fetal circulation. It participates in biosynthesis and metabolism of steroids as well as their regulated exchange between maternal and fetal compartment. This review outlines the mechanisms of human placental handling of steroid compounds. Cholesterol is transported from mother to offspring involving lipoprotein receptors such as low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SRB1) as well as ATP-binding cassette (ABC)-transporters, ABCA1 and ABCG1. Additionally, cholesterol is also a precursor for placental progesterone and estrogen synthesis. Hormone synthesis is predominantly performed by members of the cytochrome P-450 (CYP) enzyme family including CYP11A1 or CYP19A1 and hydroxysteroid dehydrogenases (HSDs) such as 3β-HSD and 17β-HSD. Placental estrogen synthesis requires delivery of sulfate-conjugated precursor molecules from fetal and maternal serum. Placental uptake of these precursors is mediated by members of the solute carrier (SLC) family including sodium-dependent organic anion transporter (SOAT), organic anion transporter 4 (OAT4), and organic anion transporting polypeptide 2B1 (OATP2B1). Maternal-fetal glucocorticoid transport has to be tightly regulated in order to ensure healthy fetal growth and development. For that purpose, the placenta expresses the enzymes 11β-HSD 1 and 2 as well as the transporter ABCB1. This article also summarizes the impact of diverse compounds and diseases on the expression level and activity of the involved transporters, receptors, and metabolizing enzymes and concludes that the regulatory mechanisms changing the physiological to a pathophysiological state are barely explored. The structure and the cellular composition of the human placental barrier are introduced. While steroid production, metabolism and transport in the placental syncytiotrophoblast have been explored for decades, few information is available for the role of placental-fetal endothelial cells in these processes. With regard to placental structure and function, significant differences exist between species. To further decipher physiologic pathways and their pathologic alterations in placental steroid handling, proper model systems are mandatory.
孕激素、雌激素、雄激素和糖皮质激素等甾体激素及其前体胆固醇对于成功建立和维持妊娠以及胎儿的正常发育是必需的。人胎盘形成于母体和胎儿循环的界面处。它参与甾体的生物合成和代谢以及它们在母体和胎儿区间的调节性交换。本综述概述了人胎盘处理甾体化合物的机制。胆固醇从母体转运至子代涉及脂蛋白受体，如低密度脂蛋白受体（LDLR）和B1型清道夫受体（SRB1）以及ATP结合盒（ABC）转运蛋白ABCA1和ABCG1。此外，胆固醇也是胎盘孕酮和雌激素合成的前体。激素合成主要由细胞色素P-450（CYP）酶家族成员完成，包括CYP11A1或CYP19A1以及羟基类固醇脱氢酶（HSD），如3β-HSD和17β-HSD。胎盘雌激素合成需要从胎儿和母体血清中递送硫酸酯结合的前体分子。这些前体的胎盘摄取由溶质载体（SLC）家族成员介导，包括钠依赖性有机阴离子转运体（SOAT）、有机阴离子转运体4（OAT4）和有机阴离子转运多肽2B1（OATP2B1）。母胎糖皮质激素转运必须受到严格调节，以确保胎儿健康生长发育。为此，胎盘表达11β-HSD 1和2酶以及转运蛋白ABCB1。本文还总结了多种化合物和疾病对相关转运蛋白、受体和代谢酶表达水平和活性的影响，并得出结论，改变生理状态为病理生理状态的调节机制几乎未被探索。介绍了人胎盘屏障的结构和细胞组成。虽然胎盘合体滋养层细胞中的甾体产生、代谢和转运已经研究了几十年，但关于胎盘-胎儿内皮细胞在这些过程中的作用的信息却很少。关于胎盘结构和功能，不同物种之间存在显著差异。为了进一步解读胎盘甾体处理中的生理途径及其病理改变，合适的模型系统是必不可少的。
